Speaker
Description
Glioblastoma (GBM) is an aggressive malignant tumor arising from neuroglial progenitor cells, characterized by its remarkable ability to infiltrate healthy brain parenchyma. Multiomic studies have revealed a complex heterogeneity, identifying three distinct GBM subtypes: proneural, mesenchymal, and classical. In this study, we focused exclusively on the proneural subtype, using multiomics patients data from Wang et al. 2021 and LSD1 ChIP-Seq data (Faletti et al. 2021) in GBM#22 TICs, a tumor stem cell (TIC) model derived from a GBM proneural patient.
LSD1 is a significant epigenetic regulator in GBM TICs and its possible molecular mediators are miRNAs, a class of short non-coding RNAs with great importance and regulatory roles in tumors. Recently, also circRNA roles in cancer are acquiring more importance.
We performed an integrative multiomics analysis to identify a regulatory network composed by miRNAs, circRNAs and genes, also defining miRNAs and genes characterized by LSD1 peaks in their promoter regions, in order to understand their involvement in the proneural subtype.
MiRNA-Seq, RNA-Seq, and circRNA-Seq data from Wang et al. 2021 were analyzed, identifying differentially expressed miRNAs (DEMs) and genes (DEGs) between GBM proneural samples and normal samples. A Spearman anticorrelation analysis (p-value <0.05, rs < -0.6) between DEMs and DEGs was performed considering only miRNA-gene Targetscan interactions, identifying 42 significant interactions corresponding to 19 DEMs and 40 DEGs. We identified 225 circRNAs targeting these 19 DEMs using the CSCD2 database. Lastly, we verified the LSD1 presence in the DEM and DEG promoter regions and we found that 15 out of 19 DEMs and 26 out of 40 DEGs showed a LSD1 peak around their promoters.
In conclusion, we provide for the first time a regulatory network involving circRNAs in patients with proneural GBM, providing a set of regulatory interactions with miRNAs and protein coding genes that could be experimentally explored.
| Author(s) | Garavaglia C*.(1,2), Gravina T*.(1,2), Favero F. (1,2), Faletti S. (3), Osti D. (4), Pelicci G. (4) and Corà D. (1,2) |
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| Affiliation(s) | "(1) Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy. (2) Center for Translational Research on Allergic and Autoimmune Diseases (CAAD), University of Piemonte Orientale, 28100 Novara, Italy. (3) Human Technopole, Milan, Italy. (4) Department of Experimental Oncology, European Institute of Oncology (IEO), Milan 20139, Italy." |
